Effects of Dietary Interventions on Serum and Macrophage Atherogenicity
关键词
抽象
描述
Atherosclerosis is the underlying cause of cardiovascular diseases (CVD), the major cause of death worldwide. Atherosclerosis is an inflammatory disease of the arteries in which activated macrophages are abundant in the atherosclerotic lesions.
Macrophages play key roles during early atherogenesis. After differentiating from peripheral blood monocytes, the formed intimal macrophages take up oxidized/modified lipoproteins and are transformed into lipid-rich foam cells, the hallmark feature of early atherogenesis. In addition to lipoprotein uptake, lipid accumulation in macrophages can also result from alterations in cellular lipid metabolism, e.g. attenuated reverse lipid transport or enhanced rates of lipid biosynthesis. CVD and atherosclerosis development are significantly affected by nutritional factors. Although much progress has been made in understanding the role of different lipids (fatty acids, cholesterol, phospholipids or triglycerides) in atherosclerosis development and macrophage foam-cell formation, little is known about the potential impact of other nutrients, i.e. sugars or amino acids. For instance, hyperglycemia is known to enhance atherosclerosis development, and high glucose levels increases macrophage atherogenicity via pro-inflammatory and oxidative stress-related mechanisms. However, the role of monosaccharides other than glucose (fructose, galactose or mannose) and that of various disaccharides (maltose, sucrose or lactose) in macrophage foam-cell formation, the key event during early atherogenesis, is currently unknown. As for amino acids, a specific subgroup - the branched-chain amino acids (BCAAs), has recently been associated with increased CVD risk. The BCAA subgroup, composed of leucine, isoleucine, and valine, is characterized by an aliphatic structure of their side chains and by a common catabolic pathway. Recent reports have demonstrated an association between BCAAs, CVD and coronary artery disease (CAD). Serum BCAA levels have been positively associated with various CAD risk factors and with the development as well as the severity of CAD, even after controlling for other risk factors. Nevertheless, the role of BCAAs in atherosclerosis development and macrophage foam-cell formation is currently unclear. In recent decades, the availability and the consumption of various artificial sweeteners have increased considerably. In the USA for instance, approximately 30% of adults and 15% of children, report consumption of artificial sweeteners. Although the consumption of artificial sweeteners was previously associated with elevated risk for coronary heart disease (CHD), the effects of different artificial sweeteners, e.g. saccharin, aspartame, sucralose, steviol, cyclamate, and mannitol, on atherosclerosis development and their possible impact on macrophage foam-cell formation have not been investigated yet..
日期
最后验证: | 08/31/2016 |
首次提交: | 08/21/2016 |
提交的预估入学人数: | 09/07/2016 |
首次发布: | 09/08/2016 |
上次提交的更新: | 09/25/2016 |
最近更新发布: | 09/26/2016 |
实际学习开始日期: | 08/31/2016 |
预计主要完成日期: | 04/30/2018 |
预计完成日期: | 07/31/2018 |
状况或疾病
干预/治疗
Dietary Supplement: monosaccharides
Dietary Supplement: Disaccharides
Dietary Supplement: Amino acids
Dietary Supplement: Artificial Sweeteners
Other: Control
相
手臂组
臂 | 干预/治疗 |
---|---|
Sham Comparator: Control Dietary Interventions: Control- water, Flavered Chilled water, will be administered once after O.N fasting. | Other: Control Chilled water flavored with lemon juice as control |
Active Comparator: Glucose Dietary Interventions: Glucose, Monosaccharides, at the dose of 50 g, based on oral loading tests, once. | |
Experimental: Fructose Dietary Interventions: Fructose, Monosaccharides, at the dose of 50 g, once. | |
Experimental: Galactose Dietary Interventions: Monosaccharides, at the dose of 50 g, once. | |
Experimental: Mannose Dietary Interventions: Monosaccharides, at the dose of 50 g, once. | |
Experimental: Maltose Dietary Interventions: The dose of the disaccharides - 50 g, once. | |
Experimental: Sucrose Dietary Interventions: The dose of the disaccharides - 50 g, once. | |
Experimental: Lactose Dietary Interventions: The dose of the disaccharides - 50 g, once. | |
Experimental: Saccharin Dietary Interventions: The dose of the different artificial sweeteners - 300 mg, is based on an average adult male body weight of 75 kg and is set not to exceed the acceptable daily intakes of saccharin, aspartame, sucralose and steviol that were reported at 15, 50, 5, and 4 mg/kg body weight/day by the USA Food and Drug Administration, once. | |
Experimental: Aspartame Dietary Interventions: The dose of the different artificial sweeteners - 300 mg, is based on an average adult male body weight of 75 kg and is set not to exceed the acceptable daily intakes of saccharin, aspartame, sucralose and steviol that were reported at 15, 50, 5, and 4 mg/kg body weight/day by the USA Food and Drug Administration, once. | |
Experimental: Sucralose Dietary Interventions: The dose of the different artificial sweeteners - 300 mg, is based on an average adult male body weight of 75 kg and is set not to exceed the acceptable daily intakes of saccharin, aspartame, sucralose and steviol that were reported at 15, 50, 5, and 4 mg/kg body weight/day by the USA Food and Drug Administration, once. | |
Experimental: Steviol Dietary Interventions: The dose of the different artificial sweeteners - 300 mg, is based on an average adult male body weight of 75 kg and is set not to exceed the acceptable daily intakes of saccharin, aspartame, sucralose and steviol that were reported at 15, 50, 5, and 4 mg/kg body weight/day by the USA Food and Drug Administration, once. | |
Experimental: Leucine Dietary Interventions: The dose of the different BCAAs Amino acids- 5 g, is set not to exceed the mean daily intakes of leucine, isoleucine and valine for adult males that were reported at 8.64, 5.01 and 5.63 g/day, respectively, once. | |
Experimental: Isoleucine Dietary Interventions: The dose of the different BCAAs Amino acids - 5 g, is set not to exceed the mean daily intakes of leucine, isoleucine and valine for adult males that were reported at 8.64, 5.01 and 5.63 g/day, respectively, once. | |
Experimental: Valine Dietary Interventions: The dose of the different BCAAs Amino acids- 5 g, is set not to exceed the mean daily intakes of leucine, isoleucine and valine for adult males that were reported at 8.64, 5.01 and 5.63 g/day, respectively, once. |
资格标准
有资格学习的年龄 | 18 Years 至 18 Years |
有资格学习的性别 | Male |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: - Inclusion criteria will include healthy adult males between the ages of 18-50 after signing informed consent. Exclusion Criteria: - Exclusion criteria will include cardiovascular or pulmonary diseases, diabetes, cancer, morbid obesity (body mass index > 40 kg/m2), heavy smoking (> 20 cigarettes/day), or consumption of more than two alcoholic drinks per day. |
结果
主要结果指标
1. serum Oxidation dietary factors, i.e. monosaccharides, disaccharides, amino acids, or artificial atherogenicity of serum [2 years]
2. macrophages cellular Oxidation. [2 years]
次要成果指标
1. Serum lipids- Cholesterol [2 years]
2. Serum lipids- Triglycerides [2 years]
3. macrophages cellular lipids- Cholesterol [2 years]
4. macrophages cellular lipids -Triglycerides [2 years]